Trial Information

This is an exploratory non-randomized study in patients with locally advanced or metastatic
NSCLC. Patients who are eligible to apply for Extended Access Program of crizotinib must
have ALK translocation detected by RT-PCR, IHC or FISH analyses methods. Patients who
failed and progressed through at least one line of platinum containing chemotherapy and who
are older than 70 years old with failure of chemotherapy will be eligible for this study. We
will screen EML4-ALK fusion gene by RT-PCR (HotSart Taq Master Mix Kits, Qiaqen) from
patients' malignant pleural effusions and the detail was described in previous study[1]. We
will also use IHC analyses (5A4 monoclonal antibody, Novocastra) to screen ALK protein
expression in patients' FFPE tumor sections. We will further do FISH analysis by using
commercial Vysis LSI ALK Dual Color, Break Apart Rearrangement Probe (2p23) (Abott Molecular
Inc., Des Plaines, IL) to detect ALK rearrangement in positive screening tumors. Samples are
deemed to be FISH-positive if more than 15% of 50 scored tumor cells had split ALK 5' and 3'
probe signals or had isolated 3' signals[5]. Patients who have ALK rearrangement determined
in any of 3 molecular analyses methods and apply for crizotinib will receive 250mg of
crizotinib twice daily until disease progression, unacceptable toxicities or the withdrawal
of consent is noted.

Patients will be monitored carefully for the development of adverse experiences. Adverse
experiences will be evaluated according to criteria outlined in the National Cancer
Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. Patients
will also be monitored for clinical and/or radiographic evidence of disease progression
according to RECIST 1.1.

The primary endpoint of the study is overall response rate in patients with positive ALK
determined from different molecular analysis methods. The secondary endpoint included
overall response in specific subsets of patients, progression-free survival (PFS), and
overall survival (OS) at 1 year. PFS is defined as the time from day 1 of crizotinib to
disease progression or patient's death. OS was defined as the time from day 1 of crizotinib
treatment to patient's death.

During the treatment, patients will have safety measurements performed at specified time
points. Disease response will be assessed during the study by radiographic (e.g., CT or
MRI), and clinical (e.g., physical examination) evaluations, if applicable. Overall tumor
response will be assessed at the designated time points (every 12 weeks, using Response
Evaluation Criteria in Solid Tumors (RECIST, Version 1.1). The crizotinib treatment could be
continued after RECIST-defined disease progression if clinical benefit is still noted by
primary physician.

Inclusion Criteria:

1. Patient must have locally advanced or metastatic NSCLC (Stage IIIb or Stage IV by
AJCC 7th.) with positive ALK determined by RT-PCR or IHC (5A4, 3+ score). Patients
must have failed and progressed through at least one line of platinum containing
chemotherapy or failed and progressed through chemotherapy if they were older than 70
years old.

2. Patient must have at least one measurable lesion.

3. Patient is male or female and ≥ 20 years of age on the day of signing informed
consent.

4. Patient must have performance status ≤ 2 on the ECOG Performance Scale.

8. Patient, or the patient's legal representative, has voluntarily agreed to participate
by giving written informed consent.

9. Patient is able to swallow capsules and has no surgical or anatomical condition that
will preclude the patient from swallowing and absorbing oral medications on an
ongoing basis.

Exclusion Criteria:

1. Patient who has had chemotherapy within 2 weeks prior to Day 1 of Cycle 1 or has not
recovered from the adverse events due to previous agents prior to Day 1 of Cycle 1.
If the patient has residual toxicity from prior treatment, toxicity must be ≤ Grade 1
except alopecia.

2. Patient who has had major surgery within 4 weeks prior to starting of treatment or
expect major surgery in the study duration. Patient who has had prior radiotherapy
(except brain) within 1 week prior to Day 1 of Cycle 1.

3. Patient is currently participating or has participated in a study with an
investigational compound or device within 30 days, or 5x half-life from prior agents,
whichever is longer, of Day 1 of this study.

6. Patient has known hypersensitivity to the components of study drug or its analogs.

7. Patient has severe systemic disease.

8. Patient has a history or current evidence of any condition, therapy, or lab
abnormality that might confound the results of the study, interfere with the
patient's participation for the full duration of the study, or is not in the best
interest of the patient to participate, in the opinion of the treating investigator.

9. Patient has known psychiatric or substance abuse disorders that would interfere with
cooperation with the requirements of the trial.

10. Patient is, at the time of signing informed consent, a regular user (including
"recreational use") of any illicit drugs or had a recent history (within the last
year) of drug or alcohol abuse.

11. Patient is pregnant or breastfeeding, or expecting to conceive or father children
within the projected duration of the study.

12. Patient is known to be Human Immunodeficiency Virus (HIV)-positive

Start Date:

Completion Date:

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